title: Thalassemic osteopathy: a new marker of bone deposition.
abstract: Osteopathy represents a prominent cause of morbidity in patients with beta-thalassemia major (TM) and manifests as osteopenia/osteoporosis. Biochemical turnover markers (BTMs) are considered a useful, non-invasive tool for the clinical follow-up of osteoporotic patients; they can provide a dynamic view of the remodeling process and give information on the metabolic activity of bone tissue as well as on the pathogenesis of bone loss. The amino-terminal pro-peptide of type I procollagen (P1NP) is a recently introduced marker that is considered the most sensitive index of bone formation. Although demonstrated in several categories of patients with bone disease, there is little information on the clinical usefulness of this bone formation index in thalassemic patients. We evaluated the P1NP levels of 53 adult patients with b-thalassemia major (21 males and 32 females, mean age 34.5 ± 5.7, range 22-46 years) and associated osteopathy. We investigated the correlation between P1NP and bone condition as examined by dual X-ray photon absorptiometry and with BTMs expressing bone resorption and bone mineralization (carboxyterminal collagen cross-linked (CTX) terminal regions of type I collagen and osteocalcin, respectively). P1NP serum levels were correlated with CTX levels (r=0.545, p<0.001); the results were unchanged when males and females, as well as osteoporotic and osteopenic subgroups, were considered separately. No correlation was demonstrated neither between OC and CTX (r=0.17, p=ns), nor between P1NP and OC levels (r=0.11, p=ns). No correlation was demonstrated among the P1NP/CTX ratio and age, OC or densitometric values and no difference was found in the same ratio between osteopenic (0.19 ± 0.16) and osteoporotic (0.15 ± 0.14) patients. Similar results were obtained for the OC/CTX ratio, as it was not correlated with age, P1NP or densitometric values. This is the first report of circulating P1NP in patients with TM-associated osteoporosis. P1NP and CTX assays show good precision and low analytical CV, and, compared to other markers, they can acceptably reflect bone metabolic processes and promptly respond to antiosteoporotic treatments. We trust that this sensitive marker can be useful in the assessment of treatment efficacy and can overcome the pitfalls due to wide variability in the normal values of most BTMs that create difficulty in pinpointing the individual patient's response.
authors.affiliation: U.O. Medicina Interna 1A, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy; Dipartimento di Medicina Interna, Università degli Studi di Milano, Milano, Italy. Electronic address: marina.baldini@policlinico.mi.it.
authors.forename: M
authors.initials: M
authors.lastname: Baldini
authors.affiliation: U.O. Audiologia, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy. Electronic address: stella.forti@policlinico.mi.it.
authors.forename: S
authors.initials: S
authors.lastname: Forti
authors.affiliation: U.O. Medicina Interna 1A, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy; Dipartimento di Medicina Interna, Università degli Studi di Milano, Milano, Italy. Electronic address: alessandra.orsatti@unimi.it.
authors.forename: A
authors.initials: A
authors.lastname: Orsatti
authors.affiliation: U.O. Medicina Interna 1A, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy; Dipartimento di Medicina Interna, Università degli Studi di Milano, Milano, Italy. Electronic address: alessia.marcon81@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Marcon
authors.affiliation: U.O. Medicina Nucleare, Servizio di Mineralometria Ossea Computerizzata-Ambulatorio Malattie Metabolismo Minerale e Osseo, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy. Electronic address: ulivieri@policlinico.mi.it.
authors.forename: F M
authors.initials: FM
authors.lastname: Ulivieri
authors.affiliation: Dipartimento di Medicina Interna, Università degli Studi di Milano, Milano, Italy; U.O. Medicina Interna 1B, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy. Electronic address: lorena.airaghi@policlinico.mi.it.
authors.forename: L
authors.initials: L
authors.lastname: Airaghi
authors.affiliation: U.O. Medicina Interna 1A, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy; Dipartimento di Medicina Interna, Università degli Studi di Milano, Milano, Italy. Electronic address: laura.zanaboni@policlinico.mi.it.
authors.forename: L
authors.initials: L
authors.lastname: Zanaboni
authors.affiliation: U.O. Medicina Interna 1A, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, Milano, Italy; Dipartimento di Medicina Interna, Università degli Studi di Milano, Milano, Italy. Electronic address: maria.cappellini@unimi.it.
authors.forename: M D
authors.initials: MD
authors.lastname: Cappellini
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015415:Biomarkers; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000175:diagnosis / Q000209:etiology*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin
keywords: BMC; BMD; BTMs; Bone turnover; CTX; OC; Osteoporosis; P1NP; SDS; TM; Thalassemia; amino-terminal pro-peptide of type I procollagen; biochemical turnover markers; bone mineral content; bone mineral density; carboxyterminal collagen cross-linked; osteocalcin; standard deviation score; thalassemia major